CN113069531B - Hydrogel for scar-prevention skin wound repair and preparation method thereof - Google Patents
Hydrogel for scar-prevention skin wound repair and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a hydrogel for scar-proof skin wound repair, which is formed by loading anti-fibrosis polypeptide AF38pep into hydrogel formed by carboxymethyl chitosan CMCS and gamma-polyglutamic acid gamma-PGA by taking genipin as a cross-linking agent. The anti-fibrosis polypeptide AF38pep is used as a therapeutic drug, and CMCS/gamma-PGA composite hydrogel is selected as a carrier for loading the AF38pep, so that the aim of long-acting stable release of the polypeptide is fulfilled; the hydrogel has a porous structure, good swelling property and moisture retention property, is beneficial to material exchange and tissue regeneration of a wound part, and can effectively exert antibacterial property and hemostatic property of CMCS; the CMCS/gamma-PGA composite hydrogel loaded with AF38pep prepared by the invention is a multifunctional material capable of effectively inhibiting scar generation in the skin wound repair process.
Description
Belongs to the technical field of:
the invention relates to hydrogel for scar-proof skin wound repair and a preparation method thereof, in particular to hydrogel prepared from anti-fibrosis polypeptide, carboxymethyl chitosan, gamma-polyglutamic acid and genipin, belonging to the field of biomedical materials.
Background art:
the whole skin can protect the body from the external environment and can maintain homeostasis, however, the repair process of the whole skin wound is often accompanied with the generation of fibrotic diseases, and particularly, the occurrence of keloids and hyperplastic scars greatly affects the body, the mind and the economy of people. Currently, common skin scar treatment means include surgical excision, radiotherapy, laser therapy, steroid drug injection, silica gel sheet pressing and pasting and the like, but the treatment effect is limited, and side effects such as normal skin atrophy, osteoporosis, obesity and the like of a patient are easily caused. It has been shown that the adhesion plaque signal (FA) over-activated by integrin and fibronectin extra domain A (EDA-FN) can aggravate the fibrotic diseases, so that inhibition of the FA response by integrin-associated small molecule inhibitors or antibodies has been clinically effective in treating scars. The anti-fibrosis polypeptide (AF 38 pep) has a functional region similar to that of integrin, can be combined with EDA-FN, inhibits the recognition of the integrin and the EDA-FN, and can effectively prevent the generation of a fibrosis signal related to FA, however, the AF38pep has not been researched in relevant application in the aspects of inhibiting the generation of skin scars and the like.
Based on the method, the AF38 pep-loaded composite hydrogel is prepared, and the carboxymethyl chitosan (CMCS), the gamma-polyglutamic acid (gamma-PGA) and the AF38pep are tightly crosslinked together through the genipin primary amine bond reaction. The hydrogel can stably release AF38pep, promotes normal repair of wound skin, and has a good application prospect in the aspect of inhibiting skin scar formation.
Disclosure of Invention
The hydrogel for repairing the scar-proof skin wound is formed by anti-fibrosis polypeptide AF38pep, carboxymethyl chitosan, gamma-polyglutamic acid and genipin; the specific preparation method comprises the following steps:
dissolving CMCS in distilled water at room temperature to prepare a solution with the mass volume percentage (g/mL) of 2-20%, dissolving gamma-PGA in distilled water to prepare a solution with the mass volume percentage (g/mL) of 3-30%, preparing genipin in a water bath condition of 20-60 ℃ to prepare a solution with the mass volume percentage (g/mL) of 1-10%, dissolving AF38pep in distilled water (containing 1 percent DMSO) to prepare a solution with the mass volume percentage of 0.1-10 mg/mL;
2) Mixing 0.5-10 mL of CMCS solution, 0.1-10 mL of gamma-PGA solution, 0.01-10 mL of LAF38pep solution and 0.01-10 mL of genipin solution together, and stirring at room temperature for 10-100 min to form a uniform and stable mixed system;
3) Standing the prepared mixed solution at 37 ℃ for 12-60 h to form stable hydrogel, transferring the stable hydrogel to a refrigerator at-80 ℃ for freezing overnight, and freeze-drying to form a porous sponge-shaped scaffold.
Compared with the prior art, the invention has the remarkable advantages that:
1) From a material source, AF38pep is a novel polypeptide for inhibiting the occurrence of fibrosis. Currently, there are no research and clinical reports relating to the use of AF38pep for treating fibrotic diseases, particularly inhibiting scar formation during skin wound repair. Compared with the existing clinical micromolecule inhibitor, the AF38pep has the advantages of convenient storage, obvious effect, good biocompatibility and the like. The invention utilizes AF38pep as a therapeutic drug, is used for treating skin fibrosis diseases for the first time, and has good application potential.
2) In the preparation process, the hydrogel is selected as the carrier for loading the AF38pep, so that the aim of long-acting stable release of the polypeptide is achieved, the problems that the AF38pep is easy to lose when being directly applied to the body, the utilization rate is low, the effect is limited and the like are effectively solved, and the effect of more lasting and stability can be exerted.
3) The hydrogel has a porous structure, good swelling property and moisture retention property, and is beneficial to material exchange and tissue regeneration of a wound part; the antibacterial property and the hemostatic property of the CMCS can be effectively exerted, and the wound repair promoting agent also has a certain effect.
Detailed Description
Example 1:
1) Dissolving CMCS in distilled water at room temperature to prepare a solution with the mass volume percentage (g/mL) of 3%, dissolving gamma-PGA in distilled water to prepare a solution with the mass volume percentage (g/mL) of 3.5%, preparing genipin in a water bath condition at 40 ℃ to prepare a solution with the mass volume percentage (g/mL) of 4%, dissolving AF38pep in distilled water (containing 1% DMSO) to prepare a solution with the mass volume percentage of 1 mg/mL;
2) Mixing 2mL of CMCS solution, 1mL of gamma-PGA solution, 0.2mLAF38pep solution and 0.1mL of genipin solution together, and stirring at room temperature for 40min to form a uniform and stable mixed system;
3) Standing the prepared mixed solution at 37 ℃ for 24h to form stable hydrogel, transferring the stable hydrogel to a refrigerator at-80 ℃ for freezing overnight, and freeze-drying to form a porous sponge scaffold.
Example 2:
1) Dissolving CMCS in distilled water at room temperature to prepare a solution with the mass volume percentage (g/mL) of 6%, dissolving gamma-PGA in distilled water to prepare a solution with the mass volume percentage (g/mL) of 7%, preparing genipin in a water bath condition at 50 ℃ to prepare a solution with the mass volume percentage (g/mL) of 1%, dissolving AF38pep in distilled water (containing 1% DMSO) to prepare a solution with the mass volume percentage of 0.5 mg/mL;
2) Mixing 1mL of CMCS solution, 0.5mL of gamma-PGA solution, 0.4mL of LAF38pep solution and 0.4mL of genipin solution together, and stirring at room temperature for 30min to form a uniform and stable mixed system;
3) Standing the prepared mixed solution at 37 ℃ for 36h to form stable hydrogel, transferring the stable hydrogel to a refrigerator at-80 ℃ for freezing overnight, and freeze-drying to form a porous sponge scaffold.
Example 3:
1) Dissolving CMCS in distilled water at room temperature to prepare a solution with a mass volume percentage (g/mL) of 12%, dissolving gamma-PGA in distilled water to prepare a solution with a mass volume percentage (g/mL) of 14%, dissolving genipin in a water bath at 60 ℃ to prepare a solution with a mass volume percentage (g/mL) of 4%, dissolving AF38pep in distilled water (containing 1 part of DMSO) to prepare a solution with a mass volume percentage of 2 mg/mL;
2) Mixing 4mL of CMCS solution, 2mL of gamma-PGA solution, 0.8mLAF38pep solution and 0.8mL of genipin solution together, and stirring at room temperature for 90min to form a uniform and stable mixed system;
3) Standing the prepared mixed solution at 37 ℃ for 48h to form stable hydrogel, transferring the stable hydrogel into a refrigerator at-80 ℃ to freeze overnight, and freeze-drying to form a porous sponge scaffold.
Claims (1)
1. A hydrogel for repairing scar skin wound is prepared from anti-fibrosis polypeptide AF38pep, carboxymethyl chitosan, gamma-polyglutamic acid and genipin;
the preparation method comprises the following steps:
1) Dissolving CMCS in distilled water at room temperature to prepare a solution with the mass volume percentage (g/mL) of 2-20%, dissolving gamma-PGA in distilled water to prepare a solution with the mass volume percentage (g/mL) of 3-30%, preparing genipin in a water bath condition of 20-60 ℃ to prepare a solution with the mass volume percentage (g/mL) of 1-10%, and dissolving AF38pep in 1-10% DMSO aqueous solution to prepare a solution with the mass volume percentage (g/mL) of 0.1-10 mg/mL;
2) Mixing 0.5-10 mL of CMCS solution in the step 1), 0.1-10 mL of gamma-PGA solution in the step 1), 0.01-10 mL of AF38pep solution in the step 1) and 0.01-10 mL of genipin solution in the step 1), and stirring at room temperature for 10-100 min to form a uniform and stable mixed system;
3) Standing the mixed system prepared in the step 2) at 37 ℃ for 12-60 h to form stable hydrogel, transferring the stable hydrogel to a refrigerator at-80 ℃ for freezing overnight, and freeze-drying to form a porous sponge-shaped scaffold.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110380295.XA CN113069531B (en) | 2021-04-09 | 2021-04-09 | Hydrogel for scar-prevention skin wound repair and preparation method thereof |
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| CN202110380295.XA CN113069531B (en) | 2021-04-09 | 2021-04-09 | Hydrogel for scar-prevention skin wound repair and preparation method thereof |
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| CN113069531A CN113069531A (en) | 2021-07-06 |
| CN113069531B true CN113069531B (en) | 2023-02-28 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623721A (en) * | 2015-02-04 | 2015-05-20 | 南开大学 | Wound healing material and preparation method thereof |
| CN105268015A (en) * | 2015-11-11 | 2016-01-27 | 南开大学 | Antibacterial hydrogel composite material and preparation method thereof |
| CN110511285A (en) * | 2019-08-27 | 2019-11-29 | 南京安吉生物科技有限公司 | A kind of recombinant fusion polypeptide and its application |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2842330A1 (en) * | 2011-07-19 | 2013-01-24 | Thrasos Innovation, Inc. | Anti-fibrotic peptides and their use in methods for treating diseases and disorders characterized by fibrosis |
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- 2021-04-09 CN CN202110380295.XA patent/CN113069531B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623721A (en) * | 2015-02-04 | 2015-05-20 | 南开大学 | Wound healing material and preparation method thereof |
| CN105268015A (en) * | 2015-11-11 | 2016-01-27 | 南开大学 | Antibacterial hydrogel composite material and preparation method thereof |
| CN110511285A (en) * | 2019-08-27 | 2019-11-29 | 南京安吉生物科技有限公司 | A kind of recombinant fusion polypeptide and its application |
Non-Patent Citations (2)
| Title |
|---|
| Design and Evaluation of a Polypeptide that Mimics the Integrin Binding Site for EDA Fibronectin to Block Profibrotic Cell Activity;Lin Zhang et,al.;《Int. J. Mol. Sci. 》;20210204;第22卷(第4期);第2.6.多肽抑制促纤维化细胞活性的评价、第2页第2段、 讨论 * |
| 羧甲基壳聚糖水凝胶的阳离子质量分数对止血效果的影响及其止血机理;何静等;《中国科技论文》;20180623(第12期);摘要、第1326页 第一段、2.2 阳离子的质量分数、3 结论 * |
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